Combined magnetic resonance imaging and targeting device for magnetic particles

ABSTRACT

The invention relates to a combined magnetic resonance imaging and targeting device for magnetic particles having a magnetic coil array. The magnetic coil array comprises a plurality of coils, each of which is connected to a power supply. The power supplies are connected to a controller which is embodied for two operating modes. In a first operating mode the power supplies are controlled in such a way that a magnetic field extreme value is generated at at least one location in a target region. In a second operating mode the power supplies are controlled in such a way that magnetic fields having a strictly monotonously rising or falling magnetic field profile are generated in an imaging region.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority of German application No. 10 2008 049771.1 filed Sept. 30, 2008, which is incorporated by reference herein inits entirety.

FIELD OF THE INVENTION

The invention relates to a combined magnetic resonance imaging andtargeting device for magnetic particles having a magnetic coil array.

BACKGROUND OF THE INVENTION

Chemotherapy is a form of medical treatment for cancerous diseases(antineoplastic chemotherapy) or infections (anti-infectivechemotherapy, also antimicrobial chemotherapy). It uses substances whichexert their damaging effect in an optimally targeted manner on specificpathogenic cells or microorganisms and kill off the latter or inhibitthem in their growth. With this approach advantage is taken of thedifferent structure of multi-cell (human being) and single-cellorganisms (bacteria) in the treatment of bacterial infectious diseases.In the treatment of malignant tumors most of these substances exploitthe ability of the tumor cells to divide rapidly, since these cells aremore sensitive in their reaction to cell division malfunctions thanhealthy cells. However, said substances have a similar effect on healthycells with a similarly efficient ability to divide, as a result of whichside-effects such as hair loss or diarrhea can occur.

The desire to treat diseased compartments of the body completely withoutdistributing the chemotherapeutic agent in the remaining healthyorganism cannot be adequately realized using the systemic applicationroutes known in the prior art. Different regional and targetedpharmaceutical applications have been developed in the last 20 years inorder to protect healthy cells against increased exposure and achieve ahigher concentration of the active agent in the area of application,e.g. a tumor.

Magnetic guidance of pharmaceuticals, also known as drug targeting, isone possibility of targeted tumor treatment. With this approach,chemotherapeutic agents, such as e.g. cytostatic drugs, are reversiblybound to ferrofluids, which are colloidal solutions of magneticnanoparticles, and applied intravascularly. Said ferrofluids are thenconcentrated in a specific compartment of the body by exposure to anexternal magnetic field. They serve as transportation vehicles forconcentrating the bound chemotherapeutic agents in the desired targetregion via the bloodstream when a corresponding magnetic field isfocused over said region.

With many diseases it is desirable to perform diagnosis and treatmentideally simultaneously in a cohesive process without the need toreposition the patient.

SUMMARY OF THE INVENTION

The object underlying the invention is therefore to disclose a combinedtreatment and diagnostic device by means of which it is possible toguide magnetic particles to a target while at the same time performingdiagnostic monitoring.

The object is achieved according to the invention by the devicedisclosed in the claims. According thereto, the invention is realized ona combined magnetic resonance imaging and targeting device for magneticparticles having a magnetic coil array.

According to the inventive solution path, the device is characterized inthat the magnetic coil array comprises a plurality of coils, each ofwhich is connected to a power supply, that the power supplies areconnected to a controller which is embodied for two operating modes, thepower supplies being controlled in a first operating mode in such a waythat a magnetic field extreme value is generated at at least onelocation in a target region, and the power supplies being controlled ina second operating mode in such a way that a magnetic field having amagnetic field profile suitable for the imaging is generated in animaging region.

In this way a diagnostic magnetic resonance device is trained forguiding magnetic particles to a target such that it is made possible toperform a diagnosis and a targeting of magnetic particles to whichcorresponding medicines are bound in immediate succession without theneed to reposition the patient. The magnetic particles represent smallmagnetic poles on which magnetic fields, in particular inhomogeneousmagnetic fields, exert a force. With the aid of the magnetic coil arraycontained in the magnetic resonance device the magnetic particles areguided to the treatment location in the target region, the targetingbeing performed by means of special location-dependent magnetic fields.By means of the array structure it is possible to generate strictlymonotonously rising or falling field profiles, hereinafter also referredto as gradient fields, in the imaging region and the target region andin addition in the target region also field profiles having a magneticfield extreme value. The field forming is performed in all three spatialaxes, with the result that both a position encoding of the image signalsand a concentration of the magnetic particles can be achieved at adesired location in the target region. During the targeting it is alsopossible to exploit the effect that gradient fields tend to possess atranslational rather than a focusing effect, as is the case with fieldsthat have a magnetic field extreme value.

Given an appropriate localization geometry of the magnetic particles itis even possible to activate the first and second operating modessimultaneously. For example, a localization geometry that runs in anentire plane, e.g. a transversal plane, would be suitable for thesimultaneously activated operating modes.

The geometry and the profile of the target region can be drawn in anoverview image, for example graphically by way of an input device, e.g.a computer mouse. The currents to be provided by the power supplies arethen calculated on a computer as a function of the profile of the targetregion.

For the guiding of the magnetic particles to the target it is thus ofparticular advantage that magnetic resonance imaging and consequentlydiagnostic monitoring can be performed during the treatment without theneed to reposition the patient. The gradient fields necessary for theposition encoding during the imaging are generated by switching over theoperating mode of the controller. By means of the imaging it can then bechecked whether the magnetic particles have also reached the targetvolume. If this is not yet the case, the magnetic particles can berelocalized or, as the case may be, refocused in the first operatingmode of the controller. In this case, however, care should be taken toensure that the magnetic particles are not delocalized again by thegradient fields during the imaging. This can be achieved for the imagingby means of a short measuring duration and/or small amplitudes for theimaging magnetic field compared to the magnetic field for thelocalization.

A further application of the combined magnetic resonance imaging andtargeting device consists in its use in multicomponent therapy. In thiscase use is made of two reagents which are chemically inactive whenseparate from each other. When they come together, however, they react,generating heat in the process for example. With the aid of the magneticcarrier particles the first chemically inactive reagent can then beguided to the location of the tumor by magnetic targeting. Once it isfocused there, the patient is injected with the second chemicallyinactive reagent so that it can disperse in the body. When the secondreagent now meets the first reagent, a thermal, e.g. exothermic,reaction takes place, the resulting heat generation of which producesthe desired therapeutic effect, e.g. a tumor requiring to be treated isdamaged. A number of advantages result from the use of a plurality ofcomponents. For example, no time dependence exists in the targeting ofthe magnetic particles. In the case of a thermal reaction the occurringtemperature distribution can also be measured in a spatially resolvedmanner with the aid of magnetic resonance methods. Similarly, the degreeof destruction of a treated tumor can also be determined. In addition itwould also be possible to use a further substance which releases thereagent from the carrier magnetic particles again such that although thereagent still remains detectable using magnetic resonance methods (e.g.by means of molecular imaging), a delocalization due to the gradientfields cannot take place during the imaging.

The dependent claims disclose embodiment variants of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

An exemplary embodiment of the invention is explained below withreference to five figures, in which:

FIG. 1 is an overview representation showing the main components of acombined magnetic resonance imaging and targeting device having amagnetic coil array comprising a plurality of coils,

FIG. 2 is a schematic representation showing a first location-dependentprofile of the magnetic field in the z-direction,

FIG. 3 is a schematic representation showing a second location-dependentprofile of the magnetic field in the z-direction,

FIG. 4 is a schematic representation showing a third location-dependentprofile of the magnetic field in the z-direction, and

FIG. 5 is a schematic representation showing the position of a magneticfield extreme value in the patient.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 shows a combined diagnostic magnetic resonance imaging andtargeting device 100 by means of which, in addition to the magneticresonance imaging, magnetic particles can also be guided into a targetregion 101 inside a patient 102. Arranged in a tunnel-shaped interiorspace 103 of a magnet, preferably a superconducting magnet, 104 is atubular support 106 having in this case, by way of example, 11 coils108.1 to 108.11. In an imaging region 105 the magnet 104 generates ahomogeneous magnetic field in the longitudinal direction of the tubularinterior space 103. In a Cartesian coordinate system the z-axis isassigned to this direction. In this case the imaging region 105 isembodied in the shape of a sphere, the target region 101 being locatedfully within the imaging region 105.

The coils 108.1 to 108.11 comprise both saddle-coil-shaped conductorarrangements for generating location-dependent magnetic fields in the x-and y-direction and annular conductor arrangements for generatinglocation-dependent magnetic fields in the z-direction. The individualcoils 108.1 to 108.11 are each connected to a power supply 110.1 to110.11. The power supplies 110.1 to 110.11 are individually controlledby a controller 112 in multiple operating modes, as described in moredetail below.

Arranged within the tubular support 106 for the purpose of exciting andreceiving magnetic resonance signals is a high-frequency antenna 114that is connected to a high-frequency system 116. A central controller118 controls the entire operation of the combined magnetic resonanceimaging and targeting device 100. An input unit 120 permits a user toinput corresponding control commands, such as e.g. for controlling theoperating modes, the position of the target region 105, the pulsesequence to be activated for recording the image, the image recordingparameters, etc. Also present, finally, is a display unit 122 by meansof which the user inputs, the position of the target region and thegenerated magnetic resonance images can be presented to the user fortherapy monitoring purposes.

The geometry and the profile of the target region can be drawn e.g.graphically by way of the input unit 120, which includes a computermouse, for example, into an overview image presented on the display unit122. The current distribution for the coils 108.1 to 108.11 in themagnetic coil array is calculated as a function of the profile of thetarget region 101 on a host computer which is implemented e.g. in thecentral controller 118.

Except for the modified magnetic coil array having the coils 108.1 to108.11 and the power supplies 110.1 to 110.11 as well as thecorrespondingly modified controller 112 and central controller 118, thecombined magnetic resonance imaging and targeting device corresponds toa conventional diagnostic magnetic resonance device.

The coils 108.1 to 108.11 can be individually controlled in the mannerof an array by way of the power supplies 110.1 to 110.11 by means ofpredefined currents for generating the desired location-dependent andtime-variable magnetic field.

FIG. 2 shows by way of example the profile 202 of a linearlylocation-dependent magnetic field Mz in the longitudinal direction ofthe tunnel-shaped interior space 103, that is to say in the z-direction,in a first or second operating mode. In the first operating mode of themagnetic coil array, magnetic particles are guided to a target, and inthe second operating mode imaging is carried out for the purpose ofdiagnostic monitoring of the progress of the targeting. The gradientfield is used during the imaging for the position encoding of themagnetic resonance signals and during the targeting for generating atranslational movement of the magnetic particles. Gradient fields arealso used in the two other spatial directions (x- and y-axis of theCartesian coordinate system) for imaging as well as for thecorresponding generation of translational movements. The coils 108.1 to108.11 possess an appropriate design so that by means of a predefinedcurrent distribution of the currents from the power supplies 110.1 to110.11 for the individual coils 108.1 to 108.11 the desired profile ofthe magnetic fields can be generated not only in the z-direction butalso in the other two spatial directions x and y.

Essentially, a local extreme value, preferably a minimum, of themagnetic field is used for focusing the magnetic particles in the targetregion 101. In the first operating mode an inhomogeneous magnetic fieldis therefore generated having a local minimum 204 in the z-directionwith a section-wise linear profile, as shown in FIG. 3. The localminimum 204 is generated with the shown exemplary magnetic field profilein the z-direction at a specific location in the target region such thatthe magnetic particles 206 are concentrated there. The minima of themagnetic fields in the x- and y-direction are also generated analogouslyin the target region 101 (not shown here). The magnetic field profileshown in FIG. 3 possesses only one minimum. A plurality of extremevalues can also occur in order to allow more degrees of freedom in thecalculation of an optimal current distribution. For that purpose apre-focusing on a minimum is necessary. Here too, corresponding magneticfields are generated in the two other spatial directions x and y, suchthat a local minimum results in the target region 101.

For imaging purposes the zero magnetic field value of the gradient fieldis generally located in the point of origin of the Cartesian coordinatesystem, which in turn is located in the center of the imaging region105. For guiding the magnetic particles to the target region 101, themagnetic field, in particular the position of the magnetic field minimum204, can on the one hand be modified via a corresponding feeding ofcurrent to the coils 108.1 to 108.11. On the other hand the position ofthe patient 102 can also be changed by means of the patient examinationcouch in order to enable the particles introduced into the body to beconcentrated as rapidly as possible in the target region 101.

For targeting purposes FIG. 4 shows a section-wise parabolic profile 210of the magnetic field Mz in the z-direction in the first operating mode.The figure shows a parabolic local minimum 208 which comprises arelatively large target region 101. In addition there is also a magneticfield maximum 210, though this is located outside of the actual targetregion 101. Here too, location-dependent magnetic fields areadditionally generated in the other spatial directions. As FIG. 4 isintended to illustrate, the steepness of the gradient determines theextension of the target region 101 or, as the case may be, the focusingof the magnetic particles in the target region 101. In order to increasethe effectiveness of the targeting in the x- and y-direction, the basemagnetic field B₀ in the localization volume can be compensated by the zarray coils, while localization is performed in the x- and y-direction.

FIG. 5 illustrates the position of the target region 101 with thelocation-dependent magnetic fields used with the aid of a cross-section302 arranged at the location z1 in the z-direction inside the patient102. A tumor 304 is located in the cross-section 302 with its center atthe point x1, y1 and at the location z1 of the cross-section. Thedimensions of the tumor 304 are registered approximately by means of acircle with the radius R. The tumor 304 represents the target region 101for focusing magnetic particles 206, to which a drug that is to beapplied is bound. The magnetic field by means of which the magneticparticles 206 are to be focused in the tumor 304 has its minimum at thepoint x1, y1 in the cross-section 302. A magnetic field profile 306 isgenerated by means of the coils for generating a magnetic field Mxvarying in the x-direction, said magnetic field profile 306 beingembodied in a parabolic shape in its minimum 308. By means of the coilsfor generating a magnetic field Mx varying in the y-direction, amagnetic field profile 310 is generated with a minimum 312. The magneticfield profile 310 essentially has two linear sections. The magneticfield in the z-direction is embodied with a minimum at the location ofthe cross-section 302, such that the magnetic particles 206 are focusedat the location x1, y1, z1. The location-dependent magnetic fields usedare generated by means of a corresponding setting of the currents forthe individual coils 108.1 to 108.11.

1-5. (canceled)
 6. A combined magnetic resonance imaging and targetingdevice having a magnetic coil array for generating a non-stationary andtime-dependent magnetic field, comprising: a plurality of coils; aplurality of power supplies, each of the power supplies being connectedto one of the coils respectively; and a controller that controls thepower supplies in a first operating mode for generating a magnetic fieldextreme value at a location in a target region of a patient and controlsthe power supplies in a second operating mode for generating themagnetic field having a strictly monotonously rising or falling magneticfield profile in an imaging region of the patient.
 7. The combinedmagnetic resonance imaging and targeting device as claimed in claim 6,wherein the target region is overlapped with the imaging region.
 8. Thecombined magnetic resonance imaging and targeting device as claimed inclaim 6, wherein the target region is coincide with the imaging region.9. The combined magnetic resonance imaging and targeting device asclaimed in claim 6, wherein the magnetic field extreme value is a localminimum value.
 10. The combined magnetic resonance imaging and targetingdevice as claimed in claim 6, wherein the magnetic field profile islinear.
 11. The combined magnetic resonance imaging and targeting deviceas claimed in claim 6, wherein the magnetic field profile is parabolic.12. The combined magnetic resonance imaging and targeting device asclaimed in claim 6, wherein a plurality of field extreme values aregenerated in a plurality of locations in the target region and themagnetic field profile is a higher-order magnetic field profile betweenthe field extreme values.
 13. A method for generating a non-stationaryand time-dependent magnetic field by a combined magnetic resonanceimaging and targeting device having a magnetic coil array, comprising:arranging a plurality of coils in the magnetic coil array; connectingeach of the coils with one of a plurality of power supplies; controllingthe power supplies by a controller in a first operating mode forgenerating a magnetic field extreme value at a location in a targetregion of a patient; and controlling the power supplies in a secondoperating mode for generating the magnetic field having a strictlymonotonously rising or falling magnetic field profile in an imagingregion of the patient.